The present invention relates to a fungicidal composition comprising a fungicidally acceptable carrier and/or surface active agent and synergistically effective amounts of
(a) at least one azolopyrimidine of formula I 
xe2x80x83in which
R1 and R2 each independently represent hydrogen or an optionally substituted alkyl, alkenyl, alkynyl, alkadienyl, aryl, heteroaryl, cycloalkyl, bicycloalkyl or heterocyclyl group, or
R1 and R2 together with the adjacent nitrogen atom represent an optionally substituted heterocyclic ring,
R3 represents a hydrogen or a halogen atom or an alkyl group,
R4 represents hydrogen or an alkyl or aryl group,
L represents a halogen atom or an optionally substituted alkyl or alkoxy group,
A represents N or CR5, wherein R5 has the meaning given for R4, and n is 0 or an integer between 1 and 5; and
(b) and at least one fungicidal active ingredient which is capable of inhibiting the melanin biosynthesis in particular in Pyricularia oryzae the causal agent of the rice blast disease.
The fungicidal compounds of formula I are known from U.S. Pat. Nos. 4,567,263 and 5,593,996.
The class of melanin biosynthesis inhibitors (MBI) are chemical compounds which are capable of diminishing the in-vivo synthesis of melanin by inhibiting any of the reductase and/or dehydratase enzymes which are responsible for converting tetrahydroxynaphthalene into dihydroxynaphthalene. This class of compounds includes the following known compounds: carpropamid, chlobenthiazione, diclocymet, pyroquilon, phthalide, tricyclazole and certain phenoxyamides, which are known for example from EP 0 262 393 and Japanese patent application JP 5-9165-A.
However, there is no hint to combine the compounds of formula I, with a MBI. Moreover, there is no hint that such mixtures can be advantageously be used for controlling rice diseases such as rice blast and rice sheath blight and others.
Surprisingly, a strong synergy between the compounds of formula I and MBIs in field trials was found when these two compounds were in-tank mixed and when the activity of these co-formulations was compared with that of the solo formulations of each active ingredient.
A mixture of fungicides shows synergistic effect if the fungicidal activity of the mixture is larger than the sum of activities of the separately applied compounds. The expected fungicidal activity for a given mixture of two fungicides can also be calculated as follows (See Colby, S. R., xe2x80x9cCalculating synergistic and antagonistic response of herbicide combinationsxe2x80x9d, Weeds 15, pp 20-22 (1967):
EE=x+yxe2x88x92xxc2x7y/100
wherein
x is the efficacy in % compared with an untreated control upon treatment with a fungicidal active ingredient A at a dose rate a;
y is the efficacy in % compared with an untreated control upon treatment with a fungicidal active ingredient B at a dose rate b;
EE is the expected efficacy with a combination of fungicidal active ingredients A and B at a dose of a+b, respectively.
If the actual efficacy (E) exceeds the expected (calculated) one (EE), the mixture displays a synergistic effect.
The present invention includes a fungicidal composition comprising an acceptable carrier and/or surface active agent and synergistically effective amounts of at least one compound of formula I, and at least one melanin biosynthesis inhibitor (MBI).
The present invention also includes a method of controlling the growth of phytopathogenic fungi at a locus which comprises applying synergistically effective amounts of at least one azolopyrimidine of formula I and at least one MBI to the locus.
Preferred compounds of formula I include those wherein R1 and R2 together with the interjacent nitrogen atom represent an optionally substituted 6-membered heterocyclic ring, in particular a 4-methylpiperidine ring, or wherein
R1 represents a C1-6 alkyl, in particular an isopropyl group, a C1-6 haloalkyl, in particular a 2,2,2-trifluoroethyl or a 1,1,1-trifluoroprop-2-yl group, or a C3-8 cycloalkyl group, in particular a cyclopentyl or cyclohexyl group and R2 represents a hydrogen atom or a C1-6 alkyl group and/or wherein 
wherein L1 represents a halogen atom, preferably fluorine or chlorine and L2 and L3 each independently represent a hydrogen atom or a halogen atom, preferably fluorine, in particular wherein L1 represents fluorine, L2 represents hydrogen and L3 represents chlorine or wherein L1 through L3 represent fluorine, and/or wherein
Hal represents a chlorine atom.
In a particularly preferred embodiment the azolopyrimidine is the compound of formula IA 
wherein
L and n have the meaning given for formula I, and
R1 represents an alkyl or haloalkyl group,
R2 represents a hydrogen atom, or
R1 and R2 together represents an optionally substituted alkylene group having 3 to 6 carbon atoms in the main chain, in which one CH2 group may be replaced by O or NH, and
Hal denotes a halogen atom.
Particularly preferred are the following azolopyrimidines:
5-chloro-6-(2-chloro-6-fluorophenyl)-7-(4-methylpiperid-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidine coded Azoloyrimidine A,
5-chloro-6-(2-chloro-6-fluorophenyl)-7-isopropylamino-[1,2,4]triazolo[1,5-a]pyrimidine coded Azoloyrimidine B,
5-chloro-6-(2-chloro-6-fluorophenyl)-7-(2,2,2-trifluoroethylamino)-[1,2,4]triazolo[1,5-a]pyrimidine coded Azoloyrimidine C and
5-chloro-6-(2,4,6-trifluorophenyl)-7-(1,1,1-trifluoroprop-2-ylamino)-[1,2,4]triazolo[1,5-a]pyrimidine coded Azoloyrimidine D.
Preferred MBIs include carpropamid, chlobenthiazione, dicyclocymet, pyroquilon, phthalide and tricyclazole.
Furthermore, the phenoxyamides of formula II are preferred MBIs: 
wherein
R5 and R6 each independently represent a hydrogen atom or an optionally substituted alkyl group;
R7 independently represents a hydrogen atom or an optionally substituted alkyl group
R8 and R9 each independently represent a hydrogen atom or an optionally substituted alkyl or alkenyl group; or R8 and R9 together may represent an alkylene group;
Y each independently represents a halogen atom or an optionally substituted alkyl or alkenyl group or a cyano or nitro group;
m is 0 or an integer of 1, 2, 3 or 4.
Particularly preferred phenoxyamides are the compounds of formula IIA 
wherein R9, Y and m have the meaning given, in particular wherein 
in which Yxe2x80x2 represents a hydrogen atom or a methyl group and/or wherein R9 represents a C1-8-alkyl group.
Most preferred are N-(1-cyano-1,2-dimethyl-propyl)-2-(2,4-dichlorophenoxy)-propionamide, in particular a mixture of (2R)- and (2R/S)-N-(1-cyano-1,2-dimethyl-propyl)-2-(2,4-dichlorophenoxy)-propionamide coded Propionamide E and N-(1-cyano-1-ethyl-propyl)-2-(2,4-dichloro-3-methylphenoxy)-propionamide coded Propionamide F.
Preferred formulations of this invention include those comprising the following constituents:
a carrier agent;
at least one azolopyrimidine of formula I,
at least one MBI, in particular a phenoxyamide of formula II,
optionally a foam breaking agent, in particular a mixture of perfluoroalkyphosphonic acids and/or perfluoroalkylphosphinic acids, in particular Defoamer SF or Fluowett PL, which are commercially available from Clariant GmbH.
The compound of formula I and the MBI are to be applied together, in synergistically effective amounts. These synergistic mixtures exhibit an extraordinary efficacy against a broad range of phytopathogenic fungi, in particular against fungi from the classes ascomycetes, basidiomycetes and deuteromycetes. Therefore, they can be applied advantageously against rice diseases. They are systemic and may be applied as leaf, into water, seed dressing, nursery box or soil fungicides.
The mixture according to the invention may be preferably applied for controlling phytopathogenic fungi of the genera: Pyricularia, Rhizoctonia, Cochliobolus, Cercospora, Magnaporthe, Alternaria, Drechslera, Fusarium, Gerlachia, Achlya, Sclerotium, Gibberella, Mycosphaerella, Balansia, Sarocladium, Pythium, Phoma, Phytophthora, Bipolaris, Curvularia, Sarocladium, Nigrospora, Entyloma, Sclerophthora, Cylindrocladium, Gaeumannomyces, Myrothecium, Mucor, Rhizopus, Tilletia, Ustilago, Ustilaginoidea, Bipolaris, Sclerotium, Botrytis, Venturia, Erysiphe, Septoria, Puccinia, Leptosphaeria and Pseudocercosporella, in particular the species Rhizoctonia solani, Cochliobolus miyabeanus, Spharulina oryzina, Leptosphaeria slavini and Pyricularia oryzae. 
The application rate of the compound of formula I according to this invention is usually in the range of 5 to 2000 grams of active ingredient (g a.i.) per hectare, with rates between 30-500 g a.i./ha often achieving satisfactory control. The optimal rate for a specific application will depend on the crop(s) under cultivation and the predominant species of infesting fungus, and readily may be determined by established biological tests known to those skilled in the art.
In general, the preferred application rate of the compounds of formula I is in the range of 10 to 500 g a.i./ha, more preferably 30-300 g a.i./ha.
The optimal rate for the MBI will depend on the crop(s) under cultivation and the level of infestation by the fungus, and can readily be determined by established biological tests.
The ratio (by weight) of the compound of formula I to the MBI is as a rule, from 1:100 to 100:1. The preferred ratio formula I: MBI may vary, e.g., from about 1:50 to about 50:1, in particular from about 1:4 to about 4:1.
The active compounds will be formulated together in a suitable ratio according to the present invention, together with usual carriers and/or additives known in the art.
Accordingly the invention further provides a fungicidal composition which comprises a carrier and, as active ingredient, at least one compound of formula I as defined above and at least one MBI.
A method of making such a composition is also provided which comprises bringing the compound of formula I and the MBI as defined above into association with at least one carrier. It is also envisaged that different isomers or mixtures of isomers of the compound of formula I and/or the MBI may have different levels or spectra of activity and thus compositions may comprise individual isomers or mixtures of isomers.
A composition according to the invention preferably contains from 0.1% to 99.9%, preferably 0.2 to 80% by weight (w/w) of active ingredients.
A carrier in a composition according to the invention is any material with which the active ingredient is formulated to facilitate application to the locus to be treated, which may for example be a plant, seed, foliage, soil, or into the water where the plant grows, or to the roots, or to facilitate storage, transport or handling. A carrier may be a solid or a liquid, including material which is normally a gas but which has been compressed to form a liquid.
The compositions may be manufactured into, e.g., emulsion or emulsifiable concentrates, solutions, oil in water emulsions, wettable powders, soluble powders, suspension concentrates, solutions, dusts, granules, water dispersible granules, tablets, aerosols, micro-capsules, gels and other formulation types by well-established procedures. These procedures include intensive mixing and/or milling of the active ingredients with other substances, such as fillers, solvents, solid carriers, surface active compounds (surfactants), and optionally solid and/or liquid auxilaries and/or adjuvants. The form of application such as spraying, atomizing, dispersing or pouring may be chosen like the compositions according to the desired objectives and the given circumstances.
Solvents may be aromatic hydrocarbons, e.g. Solvesso(copyright) 200, substituted naphthalenes, phthalic acid esters, such as dibutyl or dioctyl phthalate, aliphatic hydrocarbons, e.g. cyclohexane or paraffins, alcohols and glycols as well as their ethers and esters, e.g. ethanol, ethyleneglycol mono- and dimethyl ether, ketones such as cyclohexanone, strongly polar solvents such as N-methyl-2-pyrrolidone, or xcex3-butyrolactone, higher alkyl pyrrolidones, e.g. n-octylpyrrolidone or cyclohexylpyrrolidone, epoxidized plant oil esters, e.g. methylated coconut or soybean oil ester and water. Mixtures of different liquids are often suitable.
Solid carriers, which may be used for dusts, wettable powders, water dispersible granules, or granules, may be mineral fillers, such as calcite, talc, kaolin, montmorillonite or attapulgite or others. The physical properties may be improved by addition of highly dispersed silica gel or polymers. Carriers for granules may be porous material, e.g. pumice, kaolin, sepiolite, bentonite; non-sorptive carriers may be calcite or sand or others. Additionally, a multitude of pre-granulated inorganic or organic materials may be used, such as dolomite or crushed plant residues.
Pesticidal compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application. The presence of small amounts of a carrier which is a surfactant facilitates this process of dilution. Thus, preferably at least one carrier in a composition according to the invention is a surfactant. For example, the composition may contain at two or more carriers, at least one of which is a surfactant.
Surfactants may be nonionic, anionic, cationic or zwitterionic substances with good dispersing, emulsifying and wetting properties depending on the nature of the compound according to general formula I to be formulated. Surfactants may also mean mixtures of individual surfactants.
Wettable powders of this invention suitably will contain 5 to 90% w/w of active ingredient and, in addition to a solid inert carrier, 3 to 10% w/w of dispersing and wetting agents and, where necessary, 0 to 10% w/w of stabilizer(s) and/or other additives such as penetrants or stickers. Dusts may be formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant, and may be diluted in the field with further solid carrier to give a composition usually containing 0.5 to 10% w/w of active ingredient. Water dispersible granules and granules may have a size between 0.15 mm and 2.0 mm and may be manufactured by a variety of techniques. Generally, these granules will contain 0.5 to 90% w/w active ingredient and 0 to 20% w/w of additives such as stabilizer, surfactants, slow release modifiers and binding agents. Emulsifiable concentrates may contain, in addition to a solvent or a mixture of solvents, 1 to 80% w/v active ingredient, 2 to 20% w/v emulsifiers and 0 to 20% w/v of other additives such as stabilizers, penetrants and corrosion inhibitors. Suspension concentrates are suitably milled so as to obtain a stable, non-sedimenting, flowable product and typically contain 5 to 75% w/v active ingredient, 0.5 to 15% w/v of dispersing agents, 0.1 to 10% w/v of suspending agents such as protective colloids and thixotropic agents, 0 to 10% w/v of other additives such as defoamers, corrosion inhibitors, stabilizers, penetrants and stickers, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salts may be dissolved in the formulation to assist in preventing sedimentation and crystalization or as antifreeze agents.
Aqueous dispersions and emulsions, for example compositions obtained by diluting the formulated product according to the invention with water, also lie within the scope of the invention.
Of particular interest in enhancing the duration of the protective activity of the compounds of this invention is the use of a carrier which will provide slow release of the pesticidal compounds into the environment of a plant which is to be protected.
The biological activity of the active ingredient can also be increased by including an adjuvant in the spray dilution. An adjuvant is defined here as a substance which can increase the biological activity of an active ingredient but is not itself significantly biologically active. The adjuvant can either be included in the formulation as a coformulant or carrier, or can be added to the spray tank together with the formulation containing the active ingredient.
As a commodity, the compositions may preferably be in a concentrated form whereas the end user generally employs diluted compositions. The compositions may be diluted to a concentration down to 0.001% of active ingredient. The doses usually are in the range from 0.01 to 10 kg a.i./ha.
Examples of formulations which can be used according to the invention are:
The formulation SC-E comprising Propionamide E is in-tank mixed with any of the other formulations SC-A, SC-B, SC-D, DC-A or DC-B which comprise the Azolopyrimidines A, B or D.
In a preferred embodiment the active ingredients are added to the tank mix together, each as a solo formulation.
Therefore, the present invention relates to a kit for the preparation of a spray mixture consisting of two separate formulations:
(i) a formulation which comprises at least one azolopyrimidine of formula I, in particular Azolopyrimidines A, B, C or D, conventional adjuvants and carriers;
(ii) a formulation which comprises at least one MBI, preferably a phenoxyamide of formula II, in particular Propionamide E or F, conventional adjuvants and carriers.
In a preferred embodiment the kit includes two bottles with dispensing means which allow easy and correct addition of the formulations (i) and (ii) to the tank mix.
The formulation SC-A/E comprising Azolopyrimidine A and Propionamide E can be used directly for preparing the tank mix according to the present invention.
A composition according to the invention preferably contains from 0.5% to 95% by weight of active ingredients.
The compositions of this invention may be diluted down to a concentration of 0.0001% of active ingredients.
The compositions of this invention can be applied to the plants or their environment simultaneous with or in succession with other active substances. These other active substances can be either fertilizers, agents which donate trace elements or other preparations which influence plant growth. However, they can also be selective herbicides, insecticides, fungicides, bactericides, nematicides, algicides, molluscicides, rodenticides, virucides, compounds inducing resistance into plants, biological control agents such as viruses, bacteria, nematodes, fungi and other microorganisms, repellents of birds and animals, and plant growth regulators, or mixtures of several of these preparations, if appropriate together with other carrier substances conventionally used in the art of formulation, surfactants or other additives which promote application.
Examples of the other fungicidal compounds are anilazine, azoxystrobin, benalaxyl, benomyl, binapacryl, bitertanol, blasticidin S, Bordeaux mixture, bromuconazole, bupirimate, captafol, captan, carbendazim, carboxin, chlorothalonil, chlozolinate, copper-containing compounds such as copper oxychloride, and copper sulfate, cycloheximide, cymoxanil, cypofuram, cyproconazole, cyprodinil, dichlofluanid, dichlone, dichloran, diclobutrazol, diclomezine, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, diniconazole, dinocap, ditalimfos, dithianon, dodemorph, dodine, edifenphos, epoxiconazole, etaconazole, ethirimol, etridiazole, famoxadone, fenapanil, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenpiclonil, fenpropidin, fenpropimorph, fentin, fentin acetate, fentin hydroxide, ferimzone, fluazinam, fludioxonil, flumetover, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, imazalil, iminoctadine, ipconazole, iprodione, iprovalicarb, isoprothiolane, kasugamycin, kitazin P, kresoxim-methyl, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methfuroxam, myclobutanil, neoasozin, nickel dimethyldithiocarbamate, nitrothalisopropyl, nuarimol, ofurace, organo mercury compounds, oxadixyl, oxycarboxin, penconazole, pencycuron, phenazineoxide, polyoxin D, polyram, probenazole, prochloraz, procymidione, propamocarb, propiconazole, propineb, pyrazophos, pyrifenox, pyrimethanil, pyroxyfur, quinomethionate, quinoxyfen, quintozene, spiroxamine, SSF-126, SSF-129, streptomycin, sulfur, tebuconazole, tecloftalame, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tolclofosmethyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tridemorph, triflumizole, triforine, triticonazole, validamycin A, vinclozolin, XRD-563, zarilamid, zineb, ziram.
Examples of insecticidal compounds are alpha-cypermethrin, benfuracarb, BPMC, buprofezine, carbosulfan, cartap, chlorfenvinphos, chlorpyrifos-methyl, cycloprothrin, cypermethrin, esfenvalerate, ethofenprox, fenpropathrin, flucythrinate, flufenoxuron, hydramethylnon, imidacloprid, isoxathion, MEP, MPP, nitenpyram, PAP, permethrin, propaphos, pymetrozine, silafluofen, tebufenozide, teflubenzuron, temephos, terbufos, tetrachlorvinphos and triazamate.
Examples of biological control agents are: Bacillus thuringiensis, Verticillium lecanii, Autographica californica NPV, Beauvaria bassiana, Ampelomyces quisqualis, Bacilis subtilis, Pseudomonas fluorescens, Steptomyces griseoviridis and Trichoderma harzianum. 
Examples of chemical agents that induce systemic acquired resistance in plants such are: isonicotinic acid or derivatives thereof, 2,2-dichloro-3,3-dimethylcyclopropylcarboxylic acid and BION.
The present invention is of wide applicability in the protection of crop and ornamental plants against fungal attack. Preferred crop is rice and in particular paddy-rice. The duration of the protection is normally dependent on the individual compound selected, and also a variety of external factors, such as climate, whose impact is normally mitigated by the use of a suitable formulation.